Final results from a phase Ib study showed that magrolimab plus azacitidine was “well tolerated with promising efficacy” in previously untreated higher-risk myelodysplastic syndromes (MDS), which can progress to acute myeloid leukemia (AML). The combination might be effective in this area of unmet patient need, including in patients with TP53-mutated MDS.
The combination of magrolimab plus azacitidine previously demonstrated durable responses in a phase Ib study of patients with TP53-mutated acute myeloid leukemia.
David A. Sallman, MD, of the Moffitt Cancer Center; Naval Daver, MD, of the MD Anderson Cancer Center; and colleagues conducted the study and published the data in the Journal of Clinical Oncology. Data from the study were previously presented during the 2022 Society of Hematologic Oncology Annual Meeting.
Magrolimab is a monoclonal antibody that blocks cluster of differentiation 47, which “promotes macrophage-mediated phagocytosis of tumor cells and is synergistic with azacitidine, which increases expression of eat-me signals” according to the authors.
The study included 95 patients with previously untreated MDS of intermediate (27%), high (52%), or very high (21%) risk per the Revised International Prognostic Scoring System. Many patients (62%) had poor-risk cytogenetics, while 26% had mutated TP53.
All patients received intravenous magrolimab 1 mg/kg as a priming dose followed by maintenance doses of 30 mg/kg once weekly or once every two weeks. Patients received azacitidine 75 mg/m2 intravenously/subcutaneously once daily on days one through seven of each 28-day cycle. The study’s primary endpoints were safety/tolerability and the complete remission (CR) rate.
The CR rate was 33%, with a median CR duration of 11.1 months. The overall response rate was 75%, with a median overall response duration of 9.8 months, and a median time of 1.9 months to response. The median progression-free survival was 11.6 months. The median overall survival (OS) was not reached with a follow-up of 17.1 months. In patients with TP53 mutations, 40% achieved a CR, with a median OS of 16.3 months.
Of the patients in the study, 36% receive an allogeneic hematopoietic stem cell transplant with a two-year OS rate of 77%.
Constipation was the most common treatment-emergent adverse event, reported in 68% of patients, while thrombocytopenia occurred in 55% and anemia occurred in 52%. The median hemoglobin change from baseline to the first postdose assessment was −0.7 g/dL.
“Magrolimab [plus] azacitidine was well tolerated with promising efficacy in patients with untreated higher-risk MDS, including those with TP53 mutations,” the study’s authors concluded. “A phase III trial of magrolimab/placebo [plus] azacitidine is ongoing.”
Sallman DA, Al Malki MM, Asch AS, et al. Magrolimab in combination with azacitidine in patients with higher-risk myelodysplastic syndromes: final results of a phase Ib study. J Clin Oncol. 2023. doi:10.1200/JCO.22.01794